A comparative evaluation of children's anxiety with the use of nitrous oxide-oxygen (N2O-O2) inhalation sedation during the administration of inferior alveolar nerve block (IANB). A total of 60 children between 3 and 12 years of age, with Frankl's behavior rating of 2-3 requiring IANB for any dental procedure were enrolled in this randomized clinical study. Group I (n = 30) received N2O and oxygen inhalation sedation at a concentration in the range of 25-50%, whereas group II (n = 30) received 100% O2 as a placebo. The physiological parameters like pulse rate, respiration, blood pressure, and O2 saturation were measured at the baseline, intraoperatively [during and after administration of local anesthesia (LA)] and postoperatively after the termination of the gases in both groups. The sedation level was measured intraoperatively (before administration of LA) using the Ramsay Sedation Score (RSS). The discomfort and anxiety were measured at the baseline, intraoperatively, and postoperatively using the Face, Legs, Activity, Cry, Consolability (FLACC) behavior scale. The data were evaluated using the statistical software International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) statistics 20.0. There was a significant difference in the FLACC scores between the two groups, intraoperatively (p-value-0.002), and postoperatively (p-value-0.049). The mean of the RSS for group I was 2.80 + 1.03, and for group II was 1.80 + 0.81. All the physiological parameters recorded were within the normal range. The use of N2O-O2 inhalation improved the anxiety levels in children while receiving the IANB and showed significant anxiolytic and sedative effects as compared to O2 inhalation. Nitrous oxide-oxygen (N2O-O2) inhalation can be used as a nonpharmacological behavior management adjunct for invasive treatments for children with utmost comfort for the child. Thomas PS, Dave BH, Shah DJ, et al. Comparative Assessment of Anxiety during Inferior Alveolar Nerve Block under Nitrous Oxide + Oxygen and Oxygen Inhalation Sedation in Children Aged 3-12 Years: A Randomized Clinical Trial. Int J Clin Pediatr Dent 2023;16(1):30-36.